Carcinomas cause millions of deaths annually. Of all cancers, colorectal cancer is the second leading cause of cancer-related deaths in the U.S. Most cases of carcinomas are incurable by chemotherapy and radiation therapy unless detected and treated in the early stages of the disease. The more advanced a cancer is when it is diagnosed; the less likely it is that therapy will be effective. Therefore, despite the advances in cancer research, there remains a need for novel antibodies useful for the early diagnosis and treatment of carcinomas of the colon, and lung.
Generally, antibodies are used as invaluable reagents in diagnostics. In fact, they have played a major role in deciphering the functions of various bio-molecules in biosynthetic pathways. They have also become the reagents of choice for identification and characterization of tumor specific antigens and have become a valuable tool in the classification of cancer. Once tumor-associated antigens have been purified from tissue extracts, such antigens can be used to elicit production of antibodies to the antigen by injection into animals. Monoclonal antibodies can then be produced. Such antibodies are useful both therapeutically and diagnostically.
In vitro diagnostic methods are known in the art and include immunohistiological detection of tumor cells (e.g., on human tissue, cells or excised tumor specimens) or serologic detection of tumor-associated antigens (e.g., in blood samples or other biological fluids). Immunohistiological techniques involve contacting a biological specimen such as a tumor tissue specimen with the antibody of the invention and then detecting the presence on the specimen of the antibody complexed to its antigen. The formation of such antibody-antigen complexes with the specimen indicates the presence of tumor cells in the tissue. Detection of the antibody on the specimen can be accomplished using techniques known in the art, such as the immunoperoxidase staining technique, the avidin-biotin (ABC) technique or immunofluorescence techniques (see Ciocca et al., Meth. Enzymol., 121:562-79 (1986); Kimball (ed.), Introduction To Immunology (2nd Ed.), pp. 113-117, Macmillan Publ. Co. (1986)).
Serologic diagnostic techniques involve the detection and quantitation of tumor-associated antigens that have been secreted or “shed” into the serum or other biological fluids of patients thought to be suffering from carcinoma. Such antigens can be detected in the body fluids using techniques known in the art such as radioimmunoassays (RIA) or enzyme-linked immunosorbent assays (ELISA) wherein an antibody reactive with the “shed” antigen is used to detect the presence of the antigen in a fluid sample (see, e.g., Uotila et al., J. Immunol. Methods, 42:11 (1981); Allum et al., “Monoclonal Antibodies in the Diagnosis and Treatment of Malignant Conditions” Surg. Ann., 18:41-64, 48-51 (1986); Sikora et al. (eds.), Monoclonal Antibodies, pp. 32-52, Blackwell Scientific Publications, (1984)).
However, in some cases, serological techniques have not produced results robust enough to be useful for cancer screening. Serum markers such as CEA, CA19-9 and CA242 have all been shown to have poor sensitivity and specificity for colon cancer. CEA was discovered in 1969 and was believed to be a sensitive and specific marker for colon cancer. However, further studies were unable to produce the original results. It was shown that at a cutoff concentration of 2.5 ug/L, CEA screening would yield a sensitivity of 30%-40% and a specificity of 87%. Utilizing these numbers, for every 1 colon cancer patient identified with a CEA-based assay there would be 250 false-positives and 60% of cancers would be missed. Due to these overall poor results these markers are not used for colon cancer screening.
For this reason Fecal Occult Blood (FOB) tests have long been the mainstay of colon cancer screening. Large randomized studies have shown that screening with serial FOB tests reduces mortality from colon cancer. Typical examples of FOB tests come in two types, the guaiac-based tests available under the trade names SKB-Hemoccult II® & Hemocult II SENSA®, and the immune-chemical tests available under the trade names SKB-HemeSelect® and Entrerix-InSure Fit®. Disadvantages of guaiac-based FOB tests include burdensome dietary restrictions, the inconvenient collection process, the limited single application sensitivity, and the costs associated with poor specificity (5-10% rate of false positives). FOB tests have sensitivity of 25%-40% and specificity of 80%-90%. While the immune-chemical based FOB tests have the advantages of improved compliance due to ease of use and no diet restrictions, sensitivity issues remain.
It is thus apparent that antibodies reactive with an antigen expressed at high levels by a variety of tumors may become useful towards an earlier diagnosis of cancers, the immunological monitoring of cancer patients, as well as for development of improved methods for therapy of cancers. It is also apparent that purified antigens associated with carcinomas derived from specific organs and tissues of the body can be of value for creating such monoclonal antibodies, as well as for creating cancer vaccines. It is also apparent that improved materials and methods for serological assays to identify the presence of cancer in humans would be valuable.